Organocatalytic Asymmetric α-Sulfenylation of 2-Substituted Indolin-3-ones: A Strategy for the Synthesis of Chiral 2,2-Disubstituted Indole-3-ones with S- and N-Containing Heteroquaternary Carbon Stereocenter

Abstract

An organocatalytic asymmetric α-sulfenylation of 2-substituted indolin-3-ones with N-(alkylthio or arylthio)succinimides has been developed for the first time using Cinchona-derived squaramide as the catalyst. Various chiral 2,2disubstituted indole-3-ones with S-and N-containing heteroquaternary carbon stereocenters were obtained with up to 98% yield and 99% ee.

Anodic C(sp3)–H Acyloxylation of Indolin-3-ones Enabled by Oxidant-Free Cross-Dehydrogenative C(sp3)–O Coupling

“…has exhibited cytotoxicity against KB and L1210 cells (Figure ). Despite their biological importance, the synthesis of indoline-like motifs with a C­(sp 3 )–O bond at C2 positions is still rare. Some strategies have been implemented, including the oxidation of indole, the bromination/nucleophilic reaction of indolin-3-ones with allyl alcohol, and the hydroxylation of indolin-3-ones, usually requiring a metal catalyst, Schmidt rearrangement conditions (NaN 3 /H 2 SO 4 ), or stoichiometric oxidants such as Br 2 , m -CPBA, or PhI­(OAc) 2 .…”

Electrochemical Oxidative Addition of Nucleophiles on 2-Arylindoles: Synthesis of C2-Heteroquaternary Indolin-3-ones

“… − This unit has also been applied as a starting material to access complex polycyclic heterocycles. − In addition, the related compounds have displayed exciting applications in optoelectronic and material science in recent years. − Due to the high synthetic and biological importance of C2-quaternary indoline-3-ones, several methods have been developed . More firmly, these methods can be broadly divided into two main categories: (i) chemoselective nucleophilic addition to preformed 2-arylindole-3-one, an activated cyclic C-acylimine (path 1, Scheme a), − and (ii) direct oxidative dearomative transformations on 2-arylindoles with various nucleophiles (path 2, Scheme a). − Additional methods − that mainly involve transition metal-catalyzed transformations − and photooxidative rearrangements − have also been developed to access this unit. Despite these existing methods, creating a more general strategy for accessing 2,2-disubstituted indolin-3-ones from 2-substituted indoles under mild conditions is highly attractive.…”

One‐Pot Asymmetric Oxidative Dearomatization of 2‐Substituted Indoles by Merging Transition Metal Catalysis with Organocatalysis to Access C2‐Tetrasubstituted Indolin‐3‐Ones

“…Due to the importance in structure, biological activity and synthetic applications, much efforts have been devoted to the synthesis of these valuable C2‐tetrasubstituted indolin‐3‐one skeletons [1e–i,2c,3–5,8–9,10a–c] . Up to now, some asymmmetric synthetic methods based on the reactivity of indolin‐3‐ones at C2 positions [4–5,10a–c] and annulation of nitroalkynes with indoles [3] have been developed to construct these C2‐ tetrasubstituted indolin‐3‐one skeletons, however, these reported methods usually require the multi‐step synthesis of starting materials or have limited substrate scope. Therefore, more efficient approach for the construction of structurally diverse C2‐tetrasubstituted indolin‐3‐ones is still highly desired.…”

“…Therefore, although significant advances have been made in the asymmetric synthesis of the valuable C2‐tetrasubstituted indolin‐3‐one skeletons based on asymmetric oxidative dearomative cascade reactions from 2‐substituted indoles, it should be noted that mild, environmentally friendly and efficient synthetic methods still need to be further developed for constructing the diversity of C2‐tetrasubstituted indolin‐3‐ones. With our ongoing interest in the study of indolin‐3‐one chemistry, [10] especially the structure of C2‐tetrasubstituted indolin‐3‐ones, [10a–c] we herein describe a one‐pot approach for the asymmetric synthesis of C2‐tetrasubstituted indolin‐3‐ones 3 from 2‐substituted indoles 1 via merging transition metal catalysis with organocatalysis. This strategy using commercially available CuI as metal‐catalyst, O 2 as green oxidant and proline as organocatalyst, undergo two processes including oxidative dearomatization of 2‐substituted indoles and proline‐promoted asymmetric Mannich reaction (Scheme 1e).…”

“…C2‐tetrasubstituted indolin‐3‐one skeletons represent an important class of structural motifs, which are existed in various natural products and biologically active molecules, [1,10b–c] such as (−)‐Isatisine A, [1a] Aristotelone, [1b–c] Austamide [1d] and Fluorocarpamine, [1e] etc . In addition, these skeletons can also be used as key intermediates in the total synthesis of many natural products, [1e,g–i,2,10b] such as Hinckdentine A, [2a–c] Lapidilectine B [2d–e] and (−)‐Trigonoliimine C, [2f–i] etc .…”